Immunocompromised patients, who include patients with
haematological malignancies (HMs), solid tumours, solid-organ transplants, human
immunodeficiency virus (HIV) or long-term corticosteroid use, are increasingly admitted
to intensive care units (ICUs). Their survival has improved markedly in recent years. For
example, most patients with HMs and acute respiratory failure (62%) and/or shock
(42%) require ICU admission. Hospital, and 90-day and 1-year post-ICU–admission
survival rates were 61%, 52%, and 43%, respectively (Azoulay et al. 2013).
Recently, among 1,004 patients with malignancies from mild (252, 25.1%), moderate
(426, 42.4%) or severe (326, 32.5%) acute respiratory distress syndrome (ARDS),
their respective mortality rates were 59%, 63% and 68.5% (p=0.06) (Azoulay et al.
2014). In addition, mortality of such populations declined from 89% in
1990–1995 to 52% in 2006–2011 (p < 0.0001). Similar trends were observed for
human immunodeficiency virus (HIV)-infected patients admitted to ICUs in a
1999–2010 multicentre cohort study in France (Barbier et al. 2014). In that cohort,
39.8% of the patients were admitted for acute respiratory failure (ARF) and
they increasingly received mechanical ventilation (rising from 42.9% to 54.0%)
over the study period. Although ICU management of immunocompromised patients
has improved for over a decade, their outcomes remain poorer than those of the
general population of ARDS patients. However, the higher numbers of immunocompromised
patients admitted to ICUs and their decreased ARDS-attributable mortality raise
the question of whether to extend and generalise the use of extracorporeal membrane
oxygenation (ECMO) to the immunocompromised (Azoulay et al. 2014). Notably, these patients are likely to develop specific ECMO-related
complications more frequently and this possibility needs to be taken into
account.

Immunocompromised patients are at risk for life-threatening
acute illness as a result of infection, toxicity of intensive treatment and targeted therapies, and decompensation of
comorbid conditions.

Bleeding

A bleeding complication is the first major risk for these
patients on ECMO, especially for those with HMs. Indeed, the ECMO device’s
non-biological surface, in the context of the patient’s underlying severe
disease, results in massive inflammatory and clotting system activation. Consequently,
anticoagulation exposes the patient to haemorrhagic complications, which are common
during ECMO management. In a review of the ECMO-associated complications of
1,763 patients, 33% of them experienced severe bleeding (Zangrillo et al. 2013).
Similarly, ECMO use during the A(H1N1) influenza pandemic was associated with
29% bleeding events (Davies et al. 2009). In a recent report on ECMO use in a
small cohort of patients with HMs, 11/14 patients were thrombocytopenic, with
their median (IQR) platelet count at 35 (26–51) G/L (Wohlfarth et al. 2014).
Although biocompatible latestgeneration ECMO devices allow reduction of the
anticoagulant dose, outcomes and overall costs are strongly impacted by
haemorrhagic complications.

Nosocomial Infection

Nosocomial infection is the second major risk for immunocompromised
patients on ECMO. Indeed, that risk on ECMO is already very high for patients
without immunodeficiency, and obviously affects outcomes. Among 220 patients
who received ECMO support for >48 hours, for a total of 2,942 ECMO-days,
142/220 (65%) developed nosocomial infections (Schmidt et al. 2012), with
ventilator associated pneumonia, bloodstream or cannula infections and
mediastinitis occurring respectively in 55%, 18%,10% and 11% of them. More
critical status at ICU admission, which includes being immunocompromised, was
associated with a subsequent risk of developing a hospital–acquired infection.

Data on Paediatric
Populations

ECMO use to counter respiratory or cardiac failure in
immunocompromised children has been limited (Di Nardo et al. 2014; Gow et al.
2009; Gow et al. 2006). Some authors have argued that patients with cancer or
endstage acquired immunodeficiency syndrome should be denied access to ECMO
(Green et al. 1995; Masiakos et al. 1999). However, overall survival rates for
this paediatric population have continued to improve over the years (Herrera et
al. 2000), and more and more clinicians are facing the challenge to implant
ECMO in these patients. According to a survey of 118 paediatric ECMO centres,
78% stated that malignancy was not a contraindication for ECMO, with only 17%
and 5%, respectively considering it a relative contraindication or who would
not offer ECMO to such patients. From 1997 to 2004 ECMO use in 107 children (73
HMs and 34 with solid tumours) was reported in the Extracorporeal Lung Support
Organization (ELSO) registry (Gow et al. 2009); it was primarily required for respiratory
support in 86 patients (80%) and lasted a median of 6.1 days. Overall survival to
hospital discharge was 35% for those with HMs or solid tumours. Although this
relatively low survival rate could be considered acceptable in light of these
patients’ notable disease severity, children with malignancies represent a wide
spectrum of disease states and outcomes. Indeed, for a subpopulation of
children undergoing haematopoietic stem-cell transplantation (HSCT), the
prognosis seemed worse. Over a 22-year period, 29 HSCT patients were entered in
the ELSO Registry: 21 (72%) required ECMO respiratory support and 8 (21%)
needed ECMO cardiac support. Twenty-three (79%) patients died on ECMO and only
3 (10%) were discharged from the hospital (Di Nardo et al. 2014). These
contrasting results, obtained for a mixed-case population of immunocompromised children,
suggest offering ECMO on a case-by-case basis, with malignancy prognosis being
an important factor.

Data on Adult
Patients

The frequency of ECMO use for immunocompromised adults is
unknown. For example, in the cohort of 2009 A(H1N1)-influenza–associated ARDS
patients treated with ECMO, 19% were immunocompromised (Pham et al. 2013),
representing 31% of the 140 cohort patients with ARDS of multiple aetiologies reported
by Schmidt et al. (2013). In that cohort, the “immunocompromised” group comprised
patients with HMs (30%), solid tumours (23%), solid-organ transplant (19%), high-dose
or long-term corticosteroid and/or immunosuppressant use (19%), and HIV infection
(9%). Only 32% were alive 6 months post-ICU admission. In addition,
immunocompromised status was independently associated with death at 6 months
post-ICU discharge (odds ratio 4.33 [95% confidence interval 1.55–12.12], p =
0.005) (Schmidt et al. 2013). Recently, Wohlfarth et al. reported the outcomes
of 14 patients with HMs who received ECMO support for severe ARF in their centre
(Wohlfarth et al. 2014). HMs were diagnosed in 4 patients during ECMO support. Five patients received their first chemotherapy dose on ECMO
and 4 had undergone HSCT within the previous year. At ICU admission, their
median (IQR) sepsis-related organ failure assessment (SOFA) score was 12
(11–13) and all patients received vasopressors; 11/14 were thrombocytopenic,
with a median platelet count of 35 (26–51) G/L, and 5 were leukocytopenic, with
a median leukocyte count of 2.1 (1.8–2.5) G/L. All HSCT recipients died, although
50% survived their ICU and hospital median (IQR) stays of 22 (21–77) days and 63
(49–110) days, respectively. Severe bleeding events were common (5/14, 36%).
Thus, clinicians must strive to avoid any increment of risk factors for bleeding
in this specific population. To achieve this goal, no or very low
anticoagulation is strongly encouraged, especially when massive platelet
transfusions are unable to restore safe platelet levels (Wohlfarth et al.
2014).

Because haemorrhage and nosocomial infections are the two
main risks for immunocompromised patients treated with ECMO, developing new
strategies to limit these risks is definitely the next stage to improve outcomes.
To reach this objective, Hoeper et al. conducted a single-centre, uncontrolled
pilot trial designed to assess the feasibility of venovenous ECMO in awake,
non-intubated, spontaneously breathing ARDS patients, thereby avoiding invasive
mechanical ventilation (Hoeper et al. 2013). Six patients with severe ARDS
(maximum PaO2/FiO2 ratios of 100 mm Hg on noninvasive ventilation), 4 of whom
were immunocompromised, were enrolled. After a mean of 7.5 days on ECMO, 4
patients were discharged from hospital; 3 of them had received ECMO alone
without invasive ventilation.

Conclusion

Using ECMO in immunocompromised patients remains
controversial due to the lack of strong scientific evidence for the benefit
that this technique might afford these patients, as they, especially adults,
develop more frequent and more severe ECMO-related complications. Pending results
of large observational or randomized trials on immunocompromised patients, ECMO
should be restricted to selected patients with at least a curative prospect of
their immunodeficiency, except those with recent (< 3 months) cardiac
transplantation, for whom it is essential. However, the markedly improved ICU
survival observed over 2 decades suggests extending ECMO use to this
population. Results of the ongoing retrospective international Immuno-Deficiency
and ECMO for Acute respiratory failure, the IDEA study (International ECMO Network
2016), should 1) provide a first detailed description of ECMO use in
immunocompromised adults with acute respiratory failure; 2) identify the major
complications arising in this specific population; and 3) describe the related
ICU, hospital and 90-day outcomes for the whole population and specific immunodeficiency
subgroups

Gow KW, Heiss KF, Wulkan ML et al. (2009) Extracorporeal
life support for support of children with malignancy and respiratory or cardiac
failure: The extracorporeal life support experience. Crit Care Med, 37(4):
1308-16. PubMed↗

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